J Pathol. 2006 Jan;208(2):152-64.
HPV-mediated cervical carcinogenesis: concepts and clinical implications.
Snijders PJ, Steenbergen RD, Heideman DA, Meijer CJ.
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Persistent infection with a high-risk human papillomavirus (hrHPV) is generally accepted as a necessary cause of cervical cancer. However, cervical cancer is a rare complication of an hrHPV infection since most such infections are transient, not even giving rise to cervical lesions. On average, it takes 12-15 years before a persistent hrHPV infection may ultimately, via consecutive premalignant stages (ie CIN lesions), lead to an overt cervical carcinoma. This argues that HPV-induced cervical carcinogenesis is multi-step in nature. In this review, the data from hrHPV-mediated in vitro transformation studies and those obtained from analysis of clinical specimens have been merged into a cervical cancer progression model. According to this model, a crucial decision maker in the early stages following infection involves individual susceptibility for certain HPV types depending on the genetic make-up of immune surveillance determinants. Once a CIN lesion has developed, altered transcriptional regulation of the viral E6/E7 oncogenes, resulting in genomic instability and distinguishing the process of cell transformation from a productive viral infection, probably provides the subsequent important step towards malignancy. The additional (epi)genetic alterations that subsequently accumulate in high-grade CIN lesions may result in overt malignancy via immortality and growth conditions that gradually become less sensitive to growth-modulating influences mediated by cytokines and cell-cell and cell-matrix adhesions. The potential implications of hrHPV testing and some other biomarkers deduced from this model for cervical screening and the clinical management of CIN disease are also discussed.
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- 1 What is cancer (malignancy)
- 2 What is meant by cancer staging?
- 3 How prevalent is cancer?
- 4 How prevalent are womens' cancers?
- 5 What causes cancer?
- 6 Is cancer a hereditary condition?
- 7 How can gynaecological cancer present?
- 8 How can we reduce the risks of the womens' cancers?
Reducing the Risks of Womens' Cancers.
- 9 What are screening tests?
- 10 What are the reactions to a diagnosis of cancer?
- 11 Is there a place for counselling when cancer is diagnosed?
- 12 Can personality alter the prognosis?
- 13 Is the incidence of deaths from the female cancers changing?
- 14 Is there a place for a holistic approach to cancer?
Cancer of the Cervix.
- 15 How prevalent is cervical cancer?
- 16 What causes cervical cancer?
- 17 How long an interval should there be between cervical screening (smear) (PAP) tests?
- 18 Is there any evidence that cervical screening can reduce the incidence of cervical cancer?
- 19 Will pre-malignant changes of the cervix invariably lead to cancer?
Endometrial Cancer (Uterus)
- 20 What causes endometrial cancer?
- 21 Are there screening tests for endometrial cancer?
- 22 How does endometrial cancer present?
Cancer of the Ovary.
- 23 How does ovarian cancer present?
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- 25 What are tumour markers?
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- 27 What is the relationship between infertility and ovarian cancer?
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- 29 What is the relationship between oral contraception and cancer?
- 30 Can ovarian cancer be prevented?
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The Treatment Of Womens' Cancers
- 14 Is there a place for a holistic approach to cancer?
- 32 Can we predict the course of a cancer?
- 33 What treatment options are available for gynaecological cancer?
- Q32.33c What treatment options are available for ovarian cancer?
Cancer of the Vulva, Vagina and Fallopian Tube
- 34 How prevalent are malignant conditions of the vulva, vagina and Fallopian tubes?
Breast Cancer
- 35 What is the incidence of breast cancer?
- 35 ?What is the cause of breast cancer?
- 35a What are the advantages of breast cancer screening - mammography - mammograms?
- 36 How often should breast screening be carried out?
- 37 Are there any problems having a mammogram?
- 38 Should I check myself for breast lumps?
- 39 One of my family developed cancer of the breast. Am I at increased risk?
- 40 We have a family tendency towards developing breast / ovarian cancer. Are there any genetic tests to find out if I am at increased risk?
- 41 What happens if a mammogram shows an abnormality?
- 42 What are the advantages and disadvantages of tamoxifen in the management of breast cancer?
- 42a Breast Cancer Treatment - What is available?
- 43 What is the relationship between breast cancer and the pill?
Web sites and Support Groups
- 44 Are there any support groups?
- 44 Are there any support groups?
- 45 Support Groups.
- 46 Breast Cancer Support Groups
- 47 Ovarian Cancer Support Groups
- 48 Endometrial Cancer Support Groups
- 49 Cervical Cancer Support Groups
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